OBJECTIVES:

Primary

• Compare the incidence and nature of cytologic changes in women with ipsilateral breast cancer vs healthy women who are and are not at increased risk for breast cancer using breast duct lavage.
• Characterize high-risk contralateral breast ductal epithelium and architecture in these women using breast duct endoscopy and correlate these findings with the incidence of cytologic changes.
• Compare the global gene expression pattern in these participants.

Secondary

• Determine the effects of estrogen replacement therapy on cytology and the gene expression profile of normal ductal epithelial cells in postmenopausal women by examining normal epithelial cells before and after initiation of estrogen replacement therapy.
• Determine the gross genomic alterations present in high risk breast epithelial cells by comparative genomic hybridization in patients with ipsilateral breast cancer.
• Determine the pattern of protein expression for selected proteins in the high-risk epithelial cells using proteomics tissue lysate arrays in these patients.

OUTLINE: Participants are stratified according to menopausal status (premenopausal vs postmenopausal).

Participants undergo breast duct lavage (in the contralateral breast for breast cancer patients and in either normal breast for healthy volunteers and high-risk subjects) and breast duct endoscopy.

Participants found to have cytologic atypia may undergo MRI and/or galactography to further localize or excise the abnormality. Participants with a cytologic atypia not suspected for malignancy undergo a follow-up lavage and endoscopy in 3-6 months.

Gene expression profiles, comparative genomic hybridization, and proteomic profiles are conducted on lavage cells.

PROJECTED ACCRUAL: A total of 110 participants (70 breast cancer patients and high-risk subjects [35 per stratum] and 40 healthy volunteers [20 per stratum]) will be accrued for this study.

DISEASE CHARACTERISTICS:

Breast cancer and high-risk subjects

• Diagnosis of unilateral breast cancer of epithelial origin (breast cancer patients)

  • Invasive or noninvasive
  • Cytologic or histologic evidence of ductal hyperplasia, atypical ductal hyperplasia, or lobular carcinoma in situ
• No breast cancer but Gail Index greater than 1.67% (high-risk subjects)

• Contralateral breast must be free of any suspicious areas by physical examination and mammogram AND without prior invasive ductal carcinoma or ductal carcinoma in situ

  • Prior atypia or lobular carcinoma in situ on biopsy is allowed
• BRCA ½ mutation carriers
• No contralateral breast prosthesis (breast cancer patients)
• No bilateral breast prosthesis (high-risk subjects)
• No prior contralateral major duct excision (breast cancer patients)
• No prior bilateral major duct excision (high-risk subjects)
• No lactating breast

Healthy volunteers

• Gail model risk index less than 1.67%
• Both breasts must be free of any suspicious areas by physical examination and mammogram (a mammogram is required only for women over 30 years of age)
• No prior atypical hyperplasia or invasive or in situ carcinoma
• No prior bilateral major duct excision
• No bilateral breast prosthesis
• No lactating breasts

PATIENT CHARACTERISTICS:

Age

• Adult

Sex

• Female

Menopausal status

• Premenopausal or postmenopausal

  • Postmenopausal defined as the absence of menstrual periods for at least 24 months
  • Postmenopausal women who have previously undergone a hysterectomy without oophorectomy must have a serum follicle-stimulating hormone greater than 40 IU/mL and a serum estradiol level of less than 40 pg/mL

Performance status

• Not specified

Life expectancy

• Not specified

Hematopoietic

• WBC greater than 2,500/mm^3
• Platelet count greater than 50,000/mm^3

Hepatic

• Not specified

Renal

• Not specified

Other

• Not pregnant
• Negative pregnancy test
• No concurrent infection

PRIOR CONCURRENT THERAPY:

Biologic therapy

• Not specified

Chemotherapy

• More than 3 months since prior chemotherapy (breast cancer patients)

Endocrine therapy

• See Disease Characteristics
• No concurrent antiestrogen therapy
• No concurrent hormone replacement therapy or oral contraceptives

Radiotherapy

• No prior radiotherapy to the contralateral breast (breast cancer patients)
• No prior therapeutic mediastinal radiotherapy (healthy volunteers or high-risk subjects)

Surgery

• See Disease Characteristics